A couple of decades after deep brain stimulation began attracting attention, treatment-resistant depression is the latest disorder that researchers think may benefit from it. Dr. Helen Mayberg, an Emory University psychiatrist and leading pioneer of the new use, talked with the Chronicle about deep brain stimulation's promise for severe depression, its potential ultimate legacy and when it could be widely available. Mayberg was in Houston this month to present grand rounds at Baylor College of Medicine and receive the school's 2013 Joan and Stanford Alexander Award in Psychiatry.

Q: What is deep brain stimulation?

A: Deep brain stimulation is a surgical procedure routinely done for severe Parkinson's disease and some other movement disorders that involves implanting electrodes in the brain, hooked to a battery implanted in the chest. It's, in essence, a pacemaker for the brain, delivering small amounts of current to a very specific location, with the goal of tuning abnormally functioning circuits.

Q: What has it shown to be effective for, and what's it still being tested for?

A: It's currently available for movement disorders, such as Parkinson's, dystonia and essential tremor, and for obsessive-compulsive disorder, for which the Food and Drug Administration has given approval under a humanitarian device exception. There are also promising results for epilepsy and, more recently, research studies for addiction, Tourette syndrome, Alzheimer's disease and depression.

Q: Is deep brain stimulation the new frontier?

A: It's part of the evolution of brain treatments for certain neuropsychiatric disorders. In the old days, before we had medications, we looked to surgically remove sick or damaged areas of the brain, which had all sorts of problems. We moved to correcting brain dysfunction with medication, very effective for certain kinds of disorders; but for many things in psychiatry and neurology, we don't have effective treatments - we're searching.

We now know the brain doesn't work as isolated regions or isolated chemicals. It works as ensembles, like an orchestra, with coordinated interactions among different areas for different functions. Identifying circuits and using electricity to tune them - the brain uses electricity to communicate - is attractive because while it's brain surgery, tuning the brain is not permanent; it's reversible. You can try a setting, and if it doesn't work, you can turn it off. You can remove the electrodes and it doesn't generally damage the brain.

Q: How is it being used for depression?

A: In patients who have severe depression and haven't responded to other treatment, we're researching what we believe is a critical brain hub within a bigger depression circuit. Activity in this circuit changes with successful responses to various treatments - psychotherapy, medication, electroconvulsive therapy. In short, when the circuit isn't properly modulated, people don't get better. We're targeting this particular hub, known as Area 25, with the hope of decreasing its overactivity; that seems to allow more normal cross talk between brain regions in the circuit. These regions working together have a critical role in the symptoms of depression, particularly the negative mood, which also impacts thinking, sleeping, appetite and other brain systems.

Q: What have been the results so far?

A: Overall so far, results for about 100 patients have been reported with implants in different brain regions. The studies average 10 to 20 patients each and involve clinical follow-up anywhere from six months to six years. There's been a response rate of roughly 40 to 60 percent, depending on the study, which is very encouraging for patients with such resistant depression. The other great thing in our experience is that in most cases, those patients who got better stayed better, which is often not the case with other therapies.

Q: How many depression patients could benefit from deep brain stimulation?

A: Estimates are difficult. Something like 7 percent of the population will have a major episode of depression at some point in their lifetime. About 40 to 60 percent will respond to treatment, although several regimens may be required. Over time, despite past treatment success, about 10 percent of patients become treatment resistant. So you're talking a lot of people. On the other hand, many people do get better with the trial and error of multiple medications and psychotherapy; it can just take time. So we probably overestimate the numbers who have the type of resistant depression for whom deep brain stimulation would be appropriate.

Q: What's the ultimate goal of deep brain stimulation research?

A: First, clearly demonstrate deep brain stimulation is effective and safe, optimize the surgery and fully understand how it works. Second, such research could eventually lead to new alternatives that are equally effective that don't involve brain surgery. Given a choice, one would clearly prefer something other than brain surgery as long as the goal is to get rid of symptoms and keep them from coming back. The more we know how deep brain stimulation works, the more we'll know about depression itself, and perhaps we can work backward to develop noninvasive electrical approaches or drugs that tune this circuit in similar specific ways.

Q: If deep brain stimulation is proved to be effective, with patients not relapsing, would you foresee people rushing to use it, like they often do for medication rather than talk therapy?

A: The choice to take a pill is a very different thing than having your brain implanted with a device that'll be there for the foreseeable future. I think you want to max out noninvasive treatments before you go to something like this. On the other hand, I see your point. To some people enslaved by depression, an invasive treatment that enables you to get well and stay well may be worth it. To lose your 20s or 30s or 40s because you are unable to find an effective treatment, resulting in the disruption of all aspects of one's life, including the high risk of death by suicide - that is pretty dire. But every potential patient needs to consider the risks and benefits. Remember, this is the early days for this experimental procedure. Relatively few patients have been implanted so it's important not to get ahead of ourselves.

Q: How much more study needs to be done before deep brain stimulation could be widely available for patients with severe depression?

A: There are lots of barriers that go into when this'll be ready for prime time, just as there are for new drugs. FDA approval is dependent on multicenter, double blind studies that prove deep brain stimulation for severe depression is safe and effective. We should know a lot more in the next few years, after the completion of a rigorous, multicenter study currently underway.